Search Results (50)

Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article

Blood-based biomarkers allow monitoring of an individual’s health status and provide insights into metabolic and inflammatory processes in conditions like obesity, cardiovascular, and liver diseases. However, selecting suitable biomarkers and optimizing analytical assays presents challenges, is time-consuming and laborious. Moreover, knowledge of potential sex differences remains incomplete as research is often carried out in men. This study aims at enabling researchers to make informed choices on the type of biomarkers, analytical assays, and dilutions being used. More specifically, we analyzed plasma concentrations of >90 biomarkers using commonly available ELISA or electrochemiluminescence-based multiplex methods, comparing normal weight (BMI < 25; n = 40) with obese (BMI > 30; n = 40) adult blood donors of comparable age. To help choose optimal biomarker sets, we grouped frequently employed biomarkers into biological categories (e.g., adipokines, acute-phase proteins, complement factors, cytokines, myokines, iron metabolism, vascular inflammation), first comparing normal-weight with obese persons, and thereafter exploratively comparing women and men within each BMI group. Many biomarkers linked to chronic inflammation and dysmetabolism were elevated in persons with obesity, including several adipokines, interleukins, chemokines, acute-phase proteins, complement factors, and oxidized LDL. Further exploration suggests sex disparities in biomarker levels within both normal-weight and obese groups. This comprehensive dataset of biomarkers across diverse biological domains constitutes a reference resource that may provide valuable guidance for researchers in selecting appropriate biomarkers and analytical assays for own studies. Moreover, the dataset highlights the importance of taking possible sex differences into account. Full article

Background/Objectives: The prognostic uncertainty of Mild Cognitive Impairment (MCI) imposes comprehensive neuropsychological evaluations beyond mere memory assessment. However, previous investigations into other cognitive domains, such as attention, have yielded divergent findings. Furthermore, while evidence suggests the presence of sex differences across the spectrum of dementia-related conditions, no study has systematically explored attentional disparities between genders within this context. The current study aims to investigate differences in the attentional subcomponents, i.e., alerting, orienting, and executive control, between patients with MCI and healthy older controls (HOCs), emphasizing interactions between biological sex and cognitive impairment. Methods: Thirty-six participants (18 MCI, and 18 HOCs) were evaluated using the Attention Network Test (ANT). Raw RTs as well as RTs corrected for general slowing were analyzed using Generalized Mixed Models. Results: Both health status and sex influenced ANT performance, when considering raw RTs. Nevertheless, after adjusting for the baseline processing speed, the effect of cognitive impairment was no longer evident in men, while it persisted in women, suggesting specific vulnerabilities in females not attributable to general slowing nor to the MCI diagnosis. Moreover, women appeared significantly slower and less accurate when dealing with conflicting information. Orienting and alerting did not differ between groups. Conclusions: To the best of our knowledge, this is the first study investigating sex differences in attentional subcomponents in the aging population. Our results suggest that previously reported inconsistencies about the decline of attentional subcomponents may be attributable to such diversities. Systematically addressing sex differences in cognitive decline appears pivotal for informing the development of precision medicine approaches. Full article

Background: Behavioral, social, and physical characteristics are posited to distinguish the sexes, yet research on transcription-level sexual differences in the brain is limited. Here, we investigated sexually divergent brain transcriptomics in pre-pubertal cynomolgus macaques, a commonly used surrogate species to humans. Methods: A transcriptomic profile using RNA sequencing was generated for the temporal lobe, ventral midbrain, and cerebellum of three female and three male cynomolgus macaques previously treated with an adeno-associated virus vector mix. Statistical analyses to determine differentially expressed protein-coding genes in all three lobes were conducted using DeSeq2 with a false-discovery-rate-corrected p-value of 0.05. Results: We identified target genes in the temporal lobe, ventral midbrain, and cerebellum with functions in translation, immunity, behavior, and neurological disorders that exhibited statistically significant sexually divergent expression. Conclusions: We provide potential mechanistic insights into the epidemiological differences observed between the sexes with regard to mental health and infectious diseases, such as COVID-19. Our results provide pre-pubertal information on sexual differences in non-human primate brain transcriptomics and may provide insight into health disparities between the biological sexes in humans. Full article

Background: Hidradenitis suppurativa (HS) is a rare, debilitating, chronic inflammatory skin disease. This study aimed to investigate differences in body composition between patients with hidradenitis suppurativa (HS) and healthy controls, with a particular focus on sex-specific disparities, while also exploring secondary associations with muscle health and quality of life. Methods: Body composition was measured using a bioanalyzer and compared between HS individuals (n = 53) and controls (n = 50). Results: The mean BMI was significantly higher in the HS group than in the controls (median 29.6 vs. median 22.1; p < 0.001, effect size −0.581). The patients with HS had a significantly higher fat mass (mean 26.2 ± 22.7 vs. 16.3 ± 6.0; p < 0.001, effect size −0.400), level of visceral fat (median 9 vs. 2; p < 0.001, effect size −0.473), percentage of total body water (mean 45.9 ± 12.3 vs. 31.9 ± 14.3; p < 0.001, effect size −0.508), skeletal muscle index (median 8.9 vs. 7.3; p < 0.001, effect size −0.445), and bone mass (median 3.2 vs. 2.5; p < 0.001, effect size −0.421); at the same time, they had a significantly lower predicted muscle mass (median 19.8 vs. 47.3; p < 0.001, effect size −0.740) and percentage of skeletal muscle mass (mean 38.2 ± 7.8 vs. 42.3 ± 5.5; p = 0.008, effect size −0.263) in comparison to the controls. The HS group was also characterized by a higher metabolic age (median 65 vs. 21 years; p < 0.001, effect size −0.760) and basal metabolic rate (median 1927 vs. 1489 kcal; p < 0.001, effect size −0.444). Conclusions: Patients with HS exhibit a distinctive pattern in body composition parameters when compared to healthy controls, which may hold significant potential for enhancing diagnostic accuracy and monitoring disease progression. This study highlighted sex-specific differences in body composition, emphasizing the need to consider biological sex in the pathophysiology and clinical evaluation of HS. Further research is needed to explore the clinical utility of body composition analysis in disease progression, therapeutic response, and personalized management. Full article

Asthma is a prevalent chronic condition, affecting an estimated 260 million people worldwide, according to the 2021 Global Burden of Disease Study. This condition significantly impacts individuals of all ages. One notable finding is that asthma prevalence among adults was higher in females than males. Recent evidence suggests that these disparities in asthma prevalence and outcomes are likely due to complex interactions among hormonal, anatomical, and environmental factors, coupled with societal and behavioral influences. The interchangeable use of the terms “sex” and “gender” in the scientific literature is frequently inconsistent. Biological sex is defined by anatomical and physiological characteristics determined by genetics; “gender”, on the other hand, is a more complex construct and a universally accepted definition is still lacking. This lack of clarity, coupled with potential knowledge gaps, misunderstandings, or the inherent difficulty in differentiating sex- and gender-related effects, often leads to the terms being poorly defined or used interchangeably. Such imprecise usage hinders accurate data interpretation and research progress. This paper provides a perspective review synthesizing current knowledge regarding the influence of sex and gender on asthma, specifically focusing on their impact on disease pathogenesis, clinical presentation, severity, and management strategies. Full article

Schizophrenia (SCZ) is a debilitating psychiatric disorder marked by alterations in cognition and social behavior, resulting in profound impacts on individuals and society. Although sex-dependent disparities in the epidemiology of SCZ are well established, the biological molecular basis of these disparities remains poorly understood. Investigating cell type-specific transcriptomic profiles is critical for identifying regulatory components underlying sex-dependent molecular dysregulation in SCZ, which could serve as targets for sex-specific therapeutic interventions. To address this, we systematically analyzed publicly available single-nucleus RNA sequencing datasets to characterize cell type-specific sex-dependent gene expression profiles in the prefrontal cortex of SCZ cases. Functional enrichment analyses revealed sex-dependent dysregulation patterns of SCZ at the pathway level. Furthermore, we constructed cell type-specific gene regulatory networks for males and females, identifying SCZ-associated transcription factors that interact with sex hormones and their receptors. By incorporating drug screening results from the Connectivity Map, we established disease–gene–drug connections, elucidating sex-dependent molecular mechanisms of SCZ from the single-gene to the regulatory network level. Our findings delineate the molecular patterns of sex-dependent disparities in SCZ, uncover regulatory mechanisms driving SCZ-associated sex-dependent dysregulation, and illustrate the signal flow through which the biological sex influences downstream cellular pathways in SCZ cases. Our study provides significant evidence supporting the neuroprotective role of estrogen in the pathophysiology of female SCZ cases, while also establishing a robust foundation for the development of sex-specific therapeutic approaches for both sexes. Full article

Background: Alzheimer’s disease (AD) is the fifth leading cause of death for Americans older than 65. Though fluctuations have been noticed over the past two decades, the mortality of Alzheimer’s patients increased considerably during the COVID-19 pandemic. This study aims to explore the temporal trends in AD-associated mortality (ADAM) and disparities in these trends, and we aim to discern changes to these trends during the COVID-19 pandemic. Methods: The CDC WONDER Multiple Cause-of-Death Public Use Records from 1999 to 2022 were used to extract population data on deaths related to AD and stratify them based on age, biological sex, race, ethnicity, place of death, census region, and state. ICD-10 codes G30.0, G30.1, G30.8, and G30.9 were used to identify AD-related mortality. Statistical analysis was performed using the Joinpoint Regression Program version 5.0.2. Results: We confirmed an increase in mortality rate in all races, sexes, places of death, age groups above 65, and states/census regions. Interestingly, the age-adjusted mortality rate (AAMR) of AD was consistently higher in females compared to males. Non-Hispanic whites had the highest AD mortality by race and ethnicity. At the intersection of race and biological sex, White females had the highest AAMR with AD. Lastly, we noted an increase in AD mortality at hospice facilities as compared to other places of death. Conclusions: Our findings demonstrate that the number of deaths due to AD was exacerbated by the recent pandemic and that White females were disproportionately affected. The disparities relating to ADAM uncovered in this study may assist healthcare administrators and policymakers in their decisions. Additionally, the findings might help initiate larger studies focusing on these disparities to explore novel risk/prognostic factors for AD. Full article

Background/Objectives: In recent years, there has been a significant increase in studies examining motor learning during preschool age and the early years of primary school. This study aimed to investigate sex differences in gross motor competence among Italian children aged 3–11 years. Methods: A convenience sample of 8500 children (mean age = 8.37 years, SD = 1.98; 50% female) was included in this cross-sectional study. Gross motor skills were assessed using the Italian version of the Test of Gross Motor Development–3, which evaluates locomotion and ball control skills. A Linear Mixed Model was applied to examine the interaction between sex and age, with school included as a random intercept and BMI as a covariate. Results: The results revealed a consistent trend of boys achieving significantly higher total scores for global motor competence (p < 0.001) across all age groups, except at age 11. Boys also demonstrated superior performance in ball control skills (p < 0.005) at all ages. In contrast, no significant differences were observed for locomotion skills overall. However, girls outperform boys in locomotor skills at ages 6, 7, and 8 (p < 0.001), with this trend disappearing by age 9. Conclusions: These findings highlight important sex-related differences in gross motor development during childhood, influenced by both biological and environmental factors. The results underscore the need for targeted interventions in educational settings to provide equitable opportunities for motor skill development, particularly for girls. Enhancing the quality of physical education and addressing gender disparities can support the acquisition of essential motor skills and promote lifelong physical activity. Full article

Background/Objectives: Alzheimer’s disease (AD) and related dementias (ADRD) disproportionately impact racial and ethnic minorities. Contributing biological factors that explain this disparity have been elusive. Moreover, non-invasive biomarkers for early detection of AD are needed. Endothelin-1 (ET-1), a vasoconstrictive factor linked to cerebral vascular disease pathology and neuronal injury, could provide insights to better understand racial disparities in AD. As a potent vasoconstrictive peptide that regulates contractions in smooth muscle, endothelial cells, and pericytes, ET-1 may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, this may result in neuronal injury, contributing to the pathology of AD. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. In the United States (U.S.), ET-1 dysregulation in Hispanic/Latinx (H/L) ethnic populations has largely been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also require further investigation. In this study, we examined the role of the ET-1 protein in human plasma as a potential biomarker with predictive value for correlating with the development of AD by age, race, and sex. Methods: We examined ET-1 protein levels using quantitative mass spectrometry in AA and NHW patients with AD, along with controls. Results: A partial correlation between age at draw and ET-1, stratified by race and sex, while controlling for AD status, was significant for female AAs (r = 0.385, p = 0.016). When the data were not stratified but controlled for AD status, the partial correlation between age at draw and ET-1 was not significant (r = 0.108, p = 0.259). Conclusions: Based on the small number of plasma specimens and no plasma specimens from H/L individuals with AD, we conclude that ET-1 was clearly not a significant factor in predicting AD in this study and will require a larger scale study for validation. Full article

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that exhibits considerable diversity in terms of both clinical and immunological manifestations. Since its female-to-male ratio is around 9:1, it is well recognized that systemic lupus erythematosus mostly affects women, especially those of childbearing age. There is a greater susceptibility to infections in adult patients with systemic lupus erythematosus (SLE) compared to the general population. However, only a small number of studies have attempted to analyze this risk using real-life data, and even fewer have successfully assessed the influence of sex. Materials and Methods: A retrospective study was conducted, enrolling patients and dividing them into two groups based on their biological sex. Infectious episodes were identified from medical records and categorized by severity. Patients were stratified according to disease duration and treatment received. Logistic regression analysis was used to calculate the odds ratio (OR), with a 95% confidence interval (CI) for the assessment of risk factors. Multivariable logistic regression was performed to adjust for potential confounders. Model fit was evaluated using the Hosmer–Lemeshow test, and interactions between variables were tested. Sensitivity analyses were conducted to assess the robustness of the findings. Results: A total of 119 patients (107 females and 12 males) were included in the analysis. No significant difference in age was found between sexes (t = −0.715, p = 0.487), but disease duration was significantly shorter in males (t = 3.35, p = 0.003). Logistic regression showed a significant association between male sex and infection risk (β = 0.9426, p = 0.05), with males having an almost sixfold higher probability of infection compared to females (OR 5.675, 95% CI: 1.4479–22.2477, p = 0.0127). Disease duration (β = 0.0250, p = 0.102) and smoking status (β = 0.4529, p = 0.078) were not statistically significant. Lastly, correlation analysis revealed a significant association between SS-A antibodies and infection rate (r = 0.291, p = 0.003). Conclusions: This study highlights a significant sex-based disparity in the risk of infections among SLE patients, with males being at a higher risk compared to females. The differences in the distribution of infections, such as the higher prevalence of pneumonia in males and urinary tract infections in females, suggest that sex-specific factors, including immunological and hormonal differences, may influence infection susceptibility. Our findings emphasize the need for tailored clinical management, with increased vigilance for infections in male patients, to improve prevention strategies and targeted therapeutic interventions in this subgroup. Full article

Laryngeal cancer is one of the main causes of morbidity and mortality worldwide, with a significantly higher prevalence among men than women. However, the incidence, clinical characteristics, and specific treatment of laryngeal cancer in women have often been overlooked by research. This review aims to examine gender differences in incidence, risk factors, hormonal mechanisms, survival, and therapeutic approaches for laryngeal cancer in women. Although smoking and alcohol remain the main risk factors, evidence suggests that women may be more vulnerable to the harmful effects of these behaviors, with a relative higher risk than men. In addition, hormonal factors such as estrogen may influence women’s susceptibility to laryngeal cancer, accelerating tumor growth and complicating treatment. Differences in treatment between the sexes, with women tending to receive less intensive treatment than men, is another crucial aspect that needs more attention. This article also analyses the disparities in survival, highlighting that women often have a better prognosis, although this trend varies according to demographic characteristics and the health system. The increasing incidence of laryngeal cancer in women requires increased research to fully understand risk factors and underlying biological mechanisms in order to develop more personalized treatments and optimize clinical outcomes for patients. Full article

Background: Sex-related treatment disparities are well-documented across various medical conditions, yet their impact on the management of inflammatory bowel disease (IBD) remains underexplored. This study aims to investigate sex-based differences in the management of ulcerative colitis (UC), focusing on both medical and surgical approaches and examining whether biological sex correlates with variations in healthcare utilization. Methods: A systematic search was conducted across multiple databases, including MEDLINE (via PubMed), Google Scholar, the Cochrane Library, and ScienceDirect, to identify studies on sex differences in ulcerative colitis (UC) management up to April 2024. Statistical analysis was performed using RevMan 5.4, with a random-effects model to combine odds ratios (OR) for both primary and secondary outcomes. The study is registered with PROSPERO (CRD42024537750). Results: The meta-analysis included eight observational studies involving 47,089 patients (51.9% females). There were no statistically significant sex differences in biologic therapy use (OR 0.89, 95% CI: 0.69 to 1.15, p = 0.36) or corticosteroid use (OR 1.17, 95% CI: 0.89 to 1.54, p = 0.27). However, females were less likely to use immunomodulators compared to males (OR 0.89, 95% CI: 0.85 to 0.94, p < 0.0001). There were no significant differences in surgical interventions, including total abdominal colectomy. Females had higher annual UC-related hospitalizations compared to males (OR 1.41, 95% CI: 1.22 to 1.64, p < 0.00001). Conclusions: In conclusion, while biologic and surgical treatments showed no significant sex differences, disparities were noted in immunomodulator use and hospitalization rates, underscoring the need for sex-specific UC management strategies. Full article

Mycotoxins, toxic secondary metabolites produced by fungi, present significant health risks through contaminated food and feed. Despite broad documentation of their general impacts, emerging research highlights the requirement of addressing both sex- and gender-specific differences in the risk of exposure, susceptibility, and health outcomes in mycotoxin screening and mitigation strategies. Distinct biological (sex-based) and sociocultural (gender-based) factors can influence the risk of mycotoxin exposure and subsequent health impacts; women may for example exhibit specific exposures to certain mycotoxins due to physiological and hormonal differences, with increased risks during critical life stages such as pregnancy and lactation. Conversely, men may demonstrate distinct metabolic and immune responses to these toxins. Socioeconomic and cultural factors also contribute to gender-specific exposure risks, including occupational exposures, dietary habits, and healthcare access. Current mycotoxin screening methodologies and regulatory frameworks often disregard these sex and gender disparities, resulting in incomplete risk assessments and suboptimal public health interventions. This review addresses the incorporation of sex- and gender-specific data into mycotoxin research, the development of advanced screening techniques, and the implementation of targeted mitigation strategies. Addressing these sex and gender differences is crucial for enhancing the efficacy of mycotoxin management policies and safeguarding public health. Future research directions and policy recommendations are discussed to promote a more comprehensive and practical approach to mycotoxin risk assessment and control. Full article

Glioblastoma (GBM) displays significant gender disparities, being 1.6 times more prevalent in men, with a median survival time of 15.0 months for males compared to 25.5 months for females. These differences may be linked to gonadal steroid hormones, particularly testosterone, which interacts with the androgen receptor (AR) to promote tumor proliferation. Conversely, estrogen (E2), progesterone (P4), and P4 metabolites exert more complex effects on GBM. Despite these insights, the identification of reliable hormonal tumor markers remains challenging, and studies investigating hormone therapies yield inconclusive results due to small sample sizes and heterogeneous tumor histology. Additionally, genetic, epigenetic, and immunological factors play critical roles in sex disparities, with female patients demonstrating increased O6-Methylguanine-DNA methyltransferase promoter methylation and greater genomic instability. These complexities highlight the need for personalized therapeutic strategies that integrate hormonal influences alongside other sex-specific biological characteristics in the management of GBM. In this review, we present the current understanding of the potential role of sex hormones in the natural history of GBM. Full article